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Heterogeneous populations of neural stem cells contribute to myelin repair

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Neural Regeneration Research 2017年第4期12卷 509-517页

作者： rainer Akkermann Felix beyer Patrick Küry Neuroregeneration Laboratory Department of NeurologyMedical FacultyHeinrich-Heine-University

As ingenious as nature＇s invention of myelin sheaths within the mammalian nervous system is, as fatal can be damage to this specialized lipid structure. Long-term loss of electrical insulation and of further supportive functions myelin provides to axons, as seen in demyelinating diseases such as multiple sclerosis （MS）, leads to neurodegeneration and results in progressive disabilities. Multiple lines of evidence have demon-strated the increasing inability of oligodendrocyte precursor cells （OPCs） to replace lost oligodendrocytes （OLs） in order to restore lost myelin. Much research has been dedicated to reveal potential reasons for this regeneration deficit but despite promising approaches no remyelination-promoting drugs have successfully been developed yet. In addition to OPCs neural stem cells of the adult central nervous system also hold a high potential to generate myelinating OLs. There are at least two neural stem cell niches in the brain, the subventricular zone lining the lateral ventricles and the subgranular zone of the dentate gyrus, and an additional source of neural stem cells has been located in the central canal of the spinal cord. While a substantial body of literature has described their neurogenic capacity, still little is known about the oligodendrogenic potential of these cells, even if some animal studies have provided proof of their contribution to remyelination. In this review, we summarize and discuss these studies, taking into account the different niches, the heterogeneity within and between stem cell niches and present current strategies of how to promote stem cell-mediated myelin repair.

关键词： heterogeneity oligodendrocyte neuroregeneration multiple sclerosis inhibitors intracellular proteinlocalization adult neural stem cell niche remyelination

Restricting carbohydrates to fight head and neck cancer——is this realistic?

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Cancer biology & Medicine 2014年第3期11卷 145-161页

作者： rainer J.Klement Department of Radiotherapy and Radiation Oncology Leopoldina Hospital

Head and neck cancers(HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates(CHOs) and their replacement with fat, mostly in form of a ketogenic diet(KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are(1) targeting the origin and specific aspects of tumor glycolysis;(2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill;(3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

关键词： Ketogenic diet(KD) head and neck neoplasms diet carbohydrate restricted(CHO restricted) nutritional support

Low-loss optical waveguides made with a high-loss material

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Light(Science & Applications) 2021年第1期10卷 12-18页

作者： Darius Urbonas rainer F.Mahrt Thilo Stoferle IbM Research Europe—Zurich Saumerstrasse 48803 RuschlikonSwitzerland

For guiding light on a chip,it has been pivotal to use materials and process flows that allow low absorption and *** on subwavelength gratings,here,we show that it is possible to create broadband,multimode waveguides with very low propagation losses despite using a strongly absorbing *** perform rigorous coupled-wave analysis and finite-difference time-domain simulations of integrated waveguides that consist of pairs of integrated high-index-contrast *** showcase this concept,we demonstrate guiding of visible light in the wavelength range of 550-650 nm with losses down to 6db/cm using silicon gratings that have a material absorption of 13,000 db/cm at this wavelength and are fabricated with standard silicon photonics *** approach allows us to overcome traditional limits of the various established photonics technology platforms with respect to their suitable spectral range and,furthermore,to mitigate situations where absorbing materials,such as highly doped semiconductors,cannot be avoided because of the need for electrical driving,for example,for amplifiers,lasers and modulators.

关键词： waveguides absorbing absorption

Association of the CLC-Kb T481S polymorphism with childhood hypertension

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Health 2010年第7期2卷 682-684页

作者： rainer büscher 不详

Essential hypertension is a difficult diagnosis in children and the gene of the renal-epithelial chloride channel ClC-Kb is potentially predisposing. In vitro studies have shown that a common ClC-Kb threonine481serine (T481S) polymorphism leads to enhanced chloride channel activity and may predispose for hypertension (HT). We therefore analysed children at risk for HT for the T481S polymorphism and associated genotype with blood pressure (bP) status. A total of 48 children with essential hypertension (mean age 14.4 ±2.7 years, 26 male;22 female;mean bP 143.4 ±7.5/88 ±5.8 mmHg) were compared with 78 children with white-coat HT (WCHT), who showed occasionally hypertensive bP values, which were not confirmed by ambulatory blood pressure monitoring (mean age 13.7 ±2.5 years, 49 male, 29 female;mean bP 122.4 ±4.3/68.2 ±3.5 mmHg). Other causes of HT were excluded. Allelic frequencies of hypertensive patients were not significantly different from those with WCHT (HT: A 0.84;T 0.16 vs. WCHT: A 0.85;T 0.15). However, the T-allele was observed more frequently in WCHT subjects with systolic and diastolic bP exceeding the 90th percentile (A 0.71;T 0.29, n = 34, p borderline hypertensive). The preliminary data suggest that children with WCHT carry the ClC-Kb T481S polymorphism more often and that this variant may predispose for development of arterial HT.

关键词： Essential Hypertension White-Coat Hypertension Ambulatory blood Pressure Monitoring (Abpm) Clc-Kb T481s Polymorphism Renal-Epithelial Chloride Channel

3omorbidity and survival of patients selected for radica prostatectomy at an age of 75 years or older

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Asian Journal of Andrology 2013年第5期15卷 667-671页

作者： Michael Froehner rainer Koch Manfred P Wirth Departments of Urology University Hospital 'Carl Gustav Carus' Dresden University of Technology Dresden D-01307 Germany Department of Medical Statistics and biometry University Hospital 'Carl Gustav Carus' Dresden University of Technology Dresden D-01307 Germany

Radical prostatectomy in elderly patients is controversial. To identify very old candidates for radical prostatectomy with the highest probability of long-term survival, we studied 47 consecutive men who underwent radical prostatectomy between 1992 and 2005 at an age of 75 years or older. A heuristic approach was used to search for subgroups with particularly high long-term survival. Several two-sided comorbidity measures and combinations of these measures were investigated to find classifications best identifying healthy, long-living elderly candidates for radical prostatectomy. Four of the 25 two-sided comorbidity classifications or combinations reached the significance level with hazard ratios between 4.00 and 4.80. After 10 years, patients identified as healthy patients according to these comorbidity measurements had exhibited relative survival rates between 129% and 137% and overall survival rates between 86% and 95%, whereas those with comorbidities had exhibited relative survival rates of only 66%-84% and overall survival rates of 44%-58%. In conclusion, classifying comorbidity may identify a meaningful proportion of men selected for radical prostatectomy at an age of 75 years or older with an excellent long-term survival probability superseding that of the general population.

关键词： comorbidity old age overall survival prostate cancer radical prostatectomy relative survival

Conserved Functions of Arabidopsis and Rice CC-Type Glutaredoxins in Flower Development and Pathogen Response

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Molecular Plant 2009年第2期2卷 323-335页

作者： ZhenWang Shuping Xing rainer R birkenbihl Sabine Zachgo Max Planck Institute for Plant breeding Research Plant Molecular Genetics 50829 Cologne Germany School of biological Sciences/Plant Science initiative University of Nebraska-Lincoln Nebraska 68588 USA botany Department University of Osnabruck 40969 Osnabruck Germany Max planck Institute for Plant breeding Research Plant Microbe Interactions 50829 Cologne Germany

Glutaredoxins （GRXs） are ubiquitous oxidoreductases that play a crucial role in response to oxidative stress by reducing disulfides in various organisms. In planta, three different GRX classes have been identified according to their active site motifs. CPYC and CGFS classes are found in all organisms, whereas the CC-type class is specific for higher land plants. Recently, two Arabidopsis CC-type GRXs, ROXY1 and ROXY2, were shown to exert crucial functions in petal and anther initiation and differentiation. To analyze the function of CC-type GRXs in the distantly related monocots, we isolated and characterized OsROXY1 and OsROXY2-two rice homologs of ROXY1. both genes are expressed in vegetative and reproductive stages. Although rice flower morphology is distinct from eudicots, OsROXY1/2 floral expression patterns are similar to their Arabidopsis counterparts ROXY1/2. Complementation experiments demonstrate that OsROXY1 and OsROXY2 can fully rescue the roxyl floral mutant phenotype. Overexpression of OsROXY1, OsROXY2, and ROXY1 in Arabidopsis causes similar vegetative and reproductive plant developmental defects. ROXY1 and its rice homologs thus exert a conserved function during eudicot and monocot flower development. Strikingly, overexpression of these CC-type GRXs also leads to an increased accumulation of hydrogen peroxide levels and hyper-susceptibility to infection from the necrotrophic pathogen botrytis cinerea, revealing the importance of balanced redox processes in flower organ develop- ment and pathogen defence.

关键词： ROXY1 glutaredoxin Arabidopsis rice flower development pathogen defence botrytis cinerea.

Level of education and mortality after radical prostatectomy

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Asian Journal of Andrology 2017年第2期19卷 173-177页

作者： Michael Froehner rainer Koch Stefan Propping Dorothea Liebeheim Matthias Hfibler Gustavo b baretton Oliver W Hakenberg Manfred P Wirth Department of Urology University Hospital 'Carl Gustav Carus' Technische Universit~t Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Medical Statistics and biometry University Hospital 'Carl Gustav Carus' Technische Universitat Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Anesthesiology University Hospital 'Carl Gustav Carus' Technische Universitat Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Pathology University Hospital 'Carl Gustav Carus' Technische Universitat Dresden Fetscherstrasse 74 D-01307 Dresden Germany Department of Urology University of Rostock Ernst-Heydemann-Strasse 6 D-18055 Rostock Germany

Estimating the risk of competing mortality is of importance in men with early prostate cancer to choose the most appropriate way of management and to avoid over- or under-treatment. In this study, we investigated the impact of the level of education in this context. The study sample consisted of 2630 patients with complete data on level of education （college, university degree, master craftsmen, comparable profession, or others）, histopathological tumor stage （organ confined or extracapsular）, lymph node status （negative or positive）, and prostatectomy specimen Gleason score （〈7, 7, or 8-10） who underwent radical prostatectomy between 1992 and 2007. Overall, prostate cancer-specific, competing, and second cancer-related mortalities were study endpoints. Cox proportional hazard models for competing risks were used to study combined effects of the variables on these endpoints. A higher level of education was independently associated with decreased overall mortality after radical prostatectomy （hazard ratio [HR]： 0.75, 95% confidence interval [95% CI]： 0.62-0.91, P = 0.0037）. The mortality difference was attributable to decreased second cancer mortality （HR： 0.59, 95% Ch 0.40-0.85, P = 0.0052） and noncancer mortality （HR： 0.73, 95% Ch 0.55-0.98, P = 0.0345） but not to differences in prostate cancer-specific mortality （HR： 1.16, 95% Ch 0.79-1.69, P = 0.4536 in the full model）. In conclusion, the level of education might serve as an independent prognostic parameter supplementary to age, comorbidity, and smoking status to estimate the risk of competing mortality and to choose optimal treatment for men with early prostate cancer who are candidates for radical prostatectomy.

关键词： comorbidity competing risk analysis level of education life expectancy mortality proportional hazards model prostate cancer radical prostatectomy smoking socioeconomic status

Effects of substrate surface treatments on hybrid manufacturing of AlSi7Mg using die casting and selective laser melting

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Journal of Materials Science & Technology 2023年第25期156卷 142-156页

作者： Haiyang Fan Ann Witvrouw Friedrich Wolf-Monheim rainer Souschek Shoufeng Yang Department of Mechanical Engineering and Flanders Make KU LeuvenCelestijnenlaan 300Bbox 2420HeverleeB-3001 LeuvenBelgium Ford Research & Advanced Engineering Ford Research and Innovation Center AachenSüsterfeldstraße 20052072 AachenGermany Yantai Research Institute Harbin Engineering University264000 YantaiChina

To balance the manufacturing cost and customizability of automotive parts,a hybrid manufacturing process combining die-casting and selective laser melting(SLM)is proposed:starting with a conventional cast substrate,SLM is utilized to add additional geometric elements on top of *** this hybrid process,the first priority is to prepare a substrate surface suitable for the subsequent SLM addition of the top-on *** this study,the original cast surface of AlSi7Mg was processed by sandblasting,wire electro-discharge machining,and laser remelting,***,additional AlSi7Mg components were built on both the original cast and treated surfaces through *** hybrid builds,these surfaces and resultant interfaces were examined by optical and scanning electron *** indicate that the defect-free metallurgical joint between the cast and additively added parts can be formed on all surfaces except for the one processed by electro-discharge *** observed epitaxial grain growth crossing the interface implies a strong connection between the cast and the SLMed *** these benefits,also mismatches in microstructure,residual stress level and element distribution between the two parts are *** a comprehensive assessment,laser remelting with no additional machining is recommended as the optimal surface treatment preceding SLM fabrication,because of its user-friendly operation,low cost,and high industrial feasibility.

关键词： Hybrid manufacturing Aluminium alloy Surface treatment Laser remelting Interface Automotive

Could a phase model help to improve translational animal research?

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Animal Models and Experimental Medicine 2022年第6期5卷 550-556页

作者： benjamin Mayer Jan Tuckermann rainer Muche Institute of Epidemiology and Medical biometry Ulm UniversityUlmGermany Institute of Comparative Molecular Endocrinology Ulm UniversityUlmGermany

background:Animal models are widely applied in medical research for different *** particular,results from translational experiments may be used for subsequent clinical ***,transferability of these findings to the human organism is *** other factors,this may be traced back to a lack of clear differentiation of the evidence(explorative ***)provided by such experimental *** general,inferential statistics(i.e.p values)should not be interpreted in as confirmatory unless crucial methodological requirements are ***:Therefore,we propose a phase model which reflects the well-established process of clinical research,and we discuss its potential to improve decision making in translational *** model aims to clarify the reliability of results derived from animal ***:The phase model proposes subdividing translational,pre-clinical research into pilot,exploration,and confirmation *** for which there is no valid estimation of the expected effect size are designated as pilot *** on these data,experiments in subsequent phases may be planned using both appropriate design and statistical ***:Separating the entire process of translational animal research into three phases could contribute to improved transparency of the evidence derived from such experiments.

关键词： confirmatory trials hypothesis testing results interpretation transferability